mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia

Yang,Guo‑Shuai; Zhou,Xiao‑Yan; An,Xue‑Fang; Liu,Xuan‑Jun; Zhang,Yan‑Jun; Yu,Dan

doi:10.3892/mmr.2018.8629

mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia

Authors:
- Guo‑Shuai Yang
- Xiao‑Yan Zhou
- Xue‑Fang An
- Xuan‑Jun Liu
- Yan‑Jun Zhang
- Dan Yu
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Affiliations: Department of Neurology, Affiliated Haikou Hospital, Xiangya School of Medicine, Central South University, Haikou, Hainan 570208, P.R. China
Published online on: February 22, 2018 https://doi.org/10.3892/mmr.2018.8629
Pages: 5821-5829
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Stroke is considered an underlying etiology of the development of seizures. Stroke leads to glucose and oxygen deficiency in neurons, resulting in brain dysfunction and injury. Mild hypothermia is a therapeutic strategy to inhibit stroke‑induced seizures, which may be associated with the regulation of energy metabolism of the brain. Mammalian target of rapamycin (mTOR) signaling and solute carrier family 2, facilitated glucose transporter member (GLUT)‑1 are critical for energy metabolism. Furthermore, mTOR overactivation and GLUT‑1 deficiency are associated with genetically acquired seizures. It has been hypothesized that mTOR and GLUT‑1 may additionally be involved in seizures elicited by stroke. The present study established global cerebral ischemia (GCI) models of rats. Convulsive seizure behaviors frequently occurred during the first and the second days following GCI, which were accompanied with seizure discharge reflected in the EEG monitor. Expression of phosphor (p)‑mTOR and GLUT‑1 were upregulated in the cerebral cortex and hippocampus, as evidenced by immunohistochemistry and western blot analyses. Mild hypothermia and/or rapamycin (mTOR inhibitor) treatments reduced the number of epileptic attacks, seizure severity scores and seizure discharges, thereby alleviating seizures induced by GCI. Mild hypothermia and/or rapamycin treatments reduced phosphorylation levels of mTOR and the downstream effecter p70S6 in neurons, and the amount of GLUT‑1 in the cytomembrane of neurons. The present study revealed that mTOR is involved in stroke‑induced seizures and the anti‑seizure effect of mild hypothermia. The role of GLUT‑1 in stroke‑elicited seizures appears to be different from the role in seizures induced by other reasons. Further studies are necessary in order to elucidate the exact function of GLUT-1 in stroke‑elicited seizures.

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